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Myeloablative ConditioningPhase 2NCT02120157

Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies

A Phase 2 study testing Cyclophosphamide, TBI and Busulfan in people with Myeloablative Conditioning and HLA-mismatched Bone Marrow Transplantation, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multi-institutional phase II haploidentical T cell replete bone marrow transplant (BMT) study in children with high-risk leukemia. The myeloablative conditioning regimen prescribed will be Total body irradiation (TBI)-based for lymphoid leukemia and busulfan-based for myeloid leukemia. Read more about this study

Who is it for?
Ages 6 months to 25 years
What is being tested?
Cyclophosphamide, TBI and Busulfan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
9 sitesin 2 countries
Study dates
2 Jul 2015to 1 Oct 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patient age 0.5-25years
  • Patients must have a first-degree related donor or half-sibling who is at minimum HLA haploidentical. The donor and recipient must be identical at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.
  • An unrelated donor search is not required for a patient to be eligible for this protocol, or a donor search and donor mobilization may be abandoned if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6-8 weeks from referral to transplant or a low-likelihood of finding a matched, unrelated donor. Patients with an eligible HLA-matched RELATED should not be enrolled on this trial.
  • Patients must have at least one of the following high-risk conditions listed below:
  • Acute lymphocytic leukemia (ALL) in CR1* as defined by at least one of the following:
  • hypodiploidy, induction failure,Minimal residual disease (MRD) after consolidation
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  • Acute myeloid leukemia (AML) in CR1 with high risk features defined as: High allelic ratio FLT3/ITD+, Monosomy 7, Del (5q), Standard risk cytogenetics with positive minimal residual disease at the end of Induction I chemotherapy (for patients being treated on or according to Children's Oncology Group (COG) AAML1031 study who have had MRD studies sent to Seattle or performed at their local institution where the flow assay is sensitive enough to detect > 0.1% blasts)
  • Acute Leukemia in 2nd or subsequent CR (CR>2)
  • Mixed phenotype/Undifferentiated Leukemia in 1st or subsequent CR*
  • Secondary or therapy related leukemia in CR > 1
  • Natural Killer (NK) cell lymphoblastic leukemia CR > 1
  • Myelodysplastic syndrome (MDS)
  • Juvenile myelomonocytic leukemia (JMML) (patients are eligible if they are not eligible for COG1221 study)
  • Prior transplant eligible if < 18yo, >6 months has elapsed since BMT, and patient is off immunosuppression for > 3 months with no Graft versus host disease (GVHD)
  • No known active Central nervous system (CNS) involvement or extramedullary involvement by malignancy. Such disease treated into remission is permitted.
  • Acute Leukemia - Remission is defined as morphology with < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > 20% cellularity.

Who cannot join

  • Poor cardiac function: left ventricular ejection fraction <45% as determined by Multigated acquisition scan (MUGA) or Echocardiogram (ECHO). For pediatric patients Left ventricular ejection fraction (LVEF) <45% or a shortening fraction below normal limits for age.
  • Symptomatic pulmonary disease. Poor pulmonary function: Forced expiratory volume (FEV1), Forced vital capacity (FVC), and Diffusing capacity for carbon monoxide (DLCO) <50% predicted (corrected for hemoglobin) for patients who have not received thoracic or mantle irradiation. For patients who have received thoracic or mantle irradiation, FEV1 and FVC <70% predicted or DLCO < 50 of predicted. For children unable to perform Pulmonary function tests (PFTs) because of developmental stage pulse oximetry < 92% on Room air (RA).
  • Poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy). Alanine aminotransferase (ALT) or Aspartate transaminase (AST) > 3 x laboratory upper normal limits.
  • Poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 60 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl) Multiply by another factor of 0.85 if female Intended for ages 18-110, serum creatinine 0.6-7 mg/dl For patients <18 years: creatinine clearance (CrCl) will be estimated by the Schwartz formula. A measured CrCl or a Glomerular filtration rate (GFR) may be substituted to determine the subject's CrCl.
  • Schwartz equation: CrCl (ml/min/1.73m2)=[length (cm) x k] /serum creatinine K = 0.45 for infants 1 to 52 weeks old k = 0.55 for children 1 to 13 years old k = 0.55 for adolescent females 13-18 years old k = 0.7 for adolescent males 13-18 years old
  • HIV-positive
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  • Positive leukocytotoxic crossmatch Specifically, complement dependent cytotoxicity and flow cytometric crossmatch assays must be negative, and the mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be <3000. Consult with PI for the clinical significance of any anti-donor antibody.
  • Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception or who are breastfeeding
  • Uncontrolled viral, bacterial, or fungal infections (currently taking medication and have progression of clinical symptoms)
  • Patients with symptoms consistent with Respiratory syncytial virus (RSV), influenza A, B, or parainfluenza at the time of enrollment will be assayed for the above viruses and if positive are not eligible for the trial until they are no longer symptomatic (patients may have continued assay positivity for a period of time post resolution of symptoms secondary to the nature of the assay

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States7 sites

  • Children's Hospital of Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21287

  • Medical University of South Carolina

    Charleston, South Carolina, 29423

  • Levine Cancer Center

    Charlotte, North Carolina, 28203

  • Washington University in St. Louis

    St Louis, Missouri, 63110

  • All Children's Hospital Johns Hopkins Medicine

    St. Petersburg, Florida, 33701

  • Nemours Alfred I. DuPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada2 sites

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

Other trials in Canada

About this study

Official title: Pediatric Blood & Marrow Transplant Consortium (PBMTC) Phase II Myeloablative Haploidentical BMT With Post-transplantation Cyclophosphamide for Pediatric Patients With Hematologic Malignancies

This is a multi-institutional phase II haploidentical T cell replete bone marrow transplant (BMT) study in children with high-risk leukemia. The myeloablative conditioning regimen prescribed will be Total body irradiation (TBI)-based for lymphoid leukemia and busulfan-based for myeloid leukemia. Our goal is to establish an easily exportable, inexpensive platform for haplotransplantation that has a safety profile equivalent to matched related and unrelated BMTs. The primary objective will be to estimate the incidence of 6-month non-relapse mortality (NRM), hypothesizing that NRM is < 18%.

Read the detailed description

This is a phase II prospective study designed to evaluate the incidence of 6 month non- relapse mortality, safety, and feasibility of haploidentical bone marrow transplantation (BMT) after myeloablative conditioning with post-transplant Cy. Conditioning regimens include a total body irradiation (TBI)-based prep for lymphoid leukemias and a chemotherapy based prep for myeloid leukemias.

To estimate the incidence of non-relapse mortality at 180 days following myeloablative haploidentical BMT for children and young adults with high risk hematologic malignancies.

Being tested
Cyclophosphamide, TBI, Busulfan, Unmanipulated Bone Marrow, Tacrolimus
Keywords
Acute lymphoblastic leukemia, Acute myeloid leukemia, Juvenile myelomonocytic leukemia, Treatment related leukemia, Biphenotypic leukemia
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Juvenile

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Cy

    Chemotherapy administration

  • TBIRadiation

    Radiation Therapy

  • BusulfanDrug

    Also called Bu

    Chemotherapy Administered

  • Unmanipulated Bone MarrowOther

    Bone Marrow Transplant

  • TacrolimusDrug

    Also called tacro

    Immunosuppressive Drug Administered

  • Mycophenolate mofetilDrug

    Also called MMF

    Immunosuppressive Drug Administered

Study groups in NCT02120157
Study groupRoleWhat they receive
Haploidentical BMT with PTCy for acute leukemias and MDSExperimentalPatients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus
Receives: Drug: Cyclophosphamide; Radiation: TBI; Drug: Busulfan; Other: Unmanipulated Bone Marrow; Drug: Tacrolimus; Drug: Mycophenolate mofetil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cumulative Incidence of Non-relapse Mortality

    Cumulative incidence (measured as a percentage) of non-relapse mortality at 180 days following myeloablative, Human Leukocyte Antigen (HLA)-mismatched bone marrow transplant (BMT) for patients with high risk hematologic malignancies.

    Measured: Day 180

Secondary outcomes (11)

  1. Number of Participants With Donor Cell Engraftment

    Number of Participants with Donor Cell Engraftment at Day 60 following myeloablative, HLA-mismatched BMT.

    Measured: Day 60

  2. Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4

    Cumulative incidence (measured as a percentage) of acute GVHD grades 2-4 (overall) and grades 3-4 (severe).

    Measured: 100 days

  3. Cumulative Incidence of Chronic GVHD

    Cumulative incidence (measured as a percentage) of chronic graft versus host disease (GVHD).

    Measured: 2 years

  4. Primary and Secondary Graft Failure

    Incidence (measured as a percentage) of primary and secondary graft failure.

    Measured: 2 years

  5. Steroid and Non-steroid Immunosuppressants

    Number of participants who used steroid and non-steroid immunosuppressants to treat GVHD.

    Measured: Two Years

  6. Steroid and Non-steroid Immunosuppressants Use Duration

    Duration of use of steroid and non-steroid immunosuppressants (in months) to treat GVHD.

    Measured: Two Years

  7. Survival

    Estimate incidence of overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), event-free survival, and relapse-free GVHD-free survival (GRFS) in patients receiving myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies at 1 year. Incidence as a percentage.

    Measured: up to 1 years

  8. Survival

    Estimate incidence of overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), event-free survival, and relapse-free GVHD-free survival (GRFS) in patients receiving myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies at 2 years. Incidence as a percentage.

    Measured: up to 2 years

  9. Immune Reconstitution

    Characterize immune reconstitution post myeloablative haploidentical BMT with Post transplantation cyclophosphamide (PT/Cy).

    Measured: Two Years

  10. Time to Neutrophil and Platelet Recovery

    Time to neutrophil and platelet recovery in median days

    Measured: 100 days

  11. Incidence of Donor Cell Engraftment

    Incidence of donor cell engraftment measured as the percentage of donor cell engraftment.

    Measured: 60 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Apr 2014 (estimated)
  2. Study start2 Jul 2015
  3. Primary completion15 Jun 2018
  4. Study completion1 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02120157
Sponsor's protocol ID
J13161
Other IDs
NA_00091665
Status last verified
Nov 2021
First submitted
16 Apr 2014
Last updated
26 Nov 2021
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Fierro-Pineda JC, Tsai HL, Blackford A, Cluster A, Caywood E, Dalal J, Davis J, Egeler M, Huo J, Hudspeth M, Keating A, Kelly SS, Krueger J, Lee D, Lehmann L, Madden L, Oshrine B, Pulsipher MA, Fry T, Symons HJ. Prospective PTCTC trial of myeloablative haplo-BMT with posttransplant cyclophosphamide for pediatric acute leukemias. Blood Adv. 2023 Sep 26;7(18):5639-5648. doi: 10.1182/bloodadvances.2023010281.

    PubMed 37257193

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, TBI and Busulfan in people with Myeloablative Conditioning and HLA-mismatched Bone Marrow Transplantation, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative Incidence of Non-relapse Mortality (time frame: Day 180). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02120157, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2021.

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